scholarly journals Role of Oxidative Stress and Inflammatory Cytokines (TNF-α and IL-6) in Acetic Acid-Induced Ulcerative Colitis in Rats: Ameliorated by Otostegia fruticosa

Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 195
Author(s):  
Mohd Nazam Ansari ◽  
Najeeb Ur Rehman ◽  
Aman Karim ◽  
Gamal A. Soliman ◽  
Majid A. Ganaie ◽  
...  

Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that causes irritation, inflammation, and ulceration in the linings of the colon and rectum. Otostegia fruticosa is traditionally used to treat various disorders in different parts of the Middle East and sub-Saharan Africa. In the present study, we evaluated the ameliorative effects of crude leaves extract of O. fruticosa (OF.Cr) on acetic acid (AA)-induced UC model in Wistar albino rats. Wistar rats were administered orally with either vehicle (10 mL/kg), OF.Cr (200 and 400 mg/kg), or prednisolone (2 mg/kg) once a day for 6 days. On day 6, UC was induced in rats by intrarectal administration of a single dose of 5% AA (1.0 mL). Disease activity index (DAI) was recorded after one day of colitis induction by assessing the symptoms of colitis and then the rats were euthanized by cervical dislocation, and colon tissues were isolated for the histopathological examination and biochemical analysis of oxidative stress parameters and cytokines (Interleukin-6 and Tumor Necrosis Factor-α). OF.Cr pretreatment exhibits significant prevention against UC, as confirmed by a significant decrease of DAI, colonic ulceration, and reduced inflammatory score as compared to the AA-induced colitis rats. Depletion of total glutathione (GSH) levels and catalase (CAT) activities in the colitis group was significantly restored in the OF.Cr treated groups, while increased lipid peroxidation in the colon tissues was significantly reduced. OF.Cr prevented the activation of the IL-6 and TNF-α pathways in the colonic tissues, which were clearly observed by the decreased levels of IL-6 and TNF-α in the OF.Cr treated animals. Hence, OF.Cr could be developed in the future for the treatment of UC.

2020 ◽  
Author(s):  
Qi-yue Yang ◽  
Ya-nan He ◽  
Le-le Ma ◽  
Run-chun Xu ◽  
Nan Li ◽  
...  

Abstract Background: Indigo naturalis is a natural dye extracted from plants and has a good anti-inflammatory effect. Clinical studies have shown that it can improve ulcerative colitis (UC), but the active constituents and the mechanism are unclear. Methods: The anti-UC activity of Indigo naturalis and its two main compounds (indigo and indirubin) were investigated in dextran sulfate sodium (DSS)-induced UC mice. Indigo naturalis, indigo and indirubin were administrated to DSS-induced UC rats by oral gavage for 1 weeks. The anti-UC effect was evaluated by pathological section, inflammatory cytokine production, western blotting, and gut microbiota analysis via 16S rRNA sequencing. Results: Indigo naturalis, indigo and indirubin can improve the UC induced by DSS. Their effect intensity is Indigo naturalis > indirubin > indigo based on disease activity index, body weight, colon length and pathological section. Indigo naturalis, indigo and indirubin also decrease the expression of NF-κB,TLR4 and MYD88 proteins, thus reducing the level of related inflammation cytokines (IL-1β, IL-6 and TNF-α) both in serum and tissue. In addition, Indigo naturalis and indigo improved symptoms of gut microbial disturbance, and decreased Firmicutes/Bacteroidetes ratio and the significantly increased probiotics such as Lactobacillus. Indirubin has little effect on the regulation of gut microbial. Conclusions: Indigo naturalis could attenuate the DSS-induced UC in mice, by means of ameliorating intestinal inflammation, improving intestinal mucosa, and regulating the disturbed gut microbiota. Indigo and indirubin could also attenuate the DSS-induced UC in mice, but their comprehensive effect is not as good as Indigo naturalis.


2019 ◽  
Vol 8 (12) ◽  
pp. 2086 ◽  
Author(s):  
Ana I. Sánchez-Garrido ◽  
Vanessa Prieto-Vicente ◽  
Víctor Blanco-Gozalo ◽  
Miguel Arévalo ◽  
Yaremi Quiros ◽  
...  

Ulcerative colitis is a relatively frequent, chronic disease that impacts significantly the patient’s quality of life. Although many therapeutic options are available, additional approaches are needed because many patients either do not respond to current therapies or show significant side effects. Cardiotrophin-1 (CT-1) is a cytokine with potent cytoprotective, anti-inflammatory, and antiapoptotic properties. The purpose of this study was to assess if the administration of CT-1 could reduce colon damage in mice with experimental colitis was induced with 5% dextran sulfate sodium (DSS) in the drinking water. Half of the mice received an i.v. dose of CT-1 (200 µg/kg) 2 h before and 2 and 4 days after DSS administration. Animals were followed during 7 days after DSS administration. The severity of colitis was measured by standard scores. Colon damage was assessed by histology and immunohistochemistry. Inflammatory mediators were measured by Western blot and PCR. CT-1 administration to DSS-treated mice ameliorated both the clinical course (disease activity index), histological damage, inflammation (colon expression of TNF-α, IL-17, IL-10, INF IFN-γ, and iNOS), and apoptosis. Our results suggest that CT-1 administration before induction of colitis improves the clinical course, tissue damage, and inflammation in DSS-induced colitis in mice.


Author(s):  
Faraza Javed ◽  
Naveed Aslam ◽  
Hafiza Maida Arshad ◽  
Ambreen Mehmood Awan ◽  
Wafa Majeed ◽  
...  

Background: Gisekia pharnaceoides Linn. (Aizoaceae), traditionally known as baluka saag or sareli is commonly found in the deep Cholistan region of Pakistan. It is used by native community for the mitigation of a range of diseases, including inflammatory disorders and gastric ulcers. Objective: This study is designed to evaluate the defensive impact of G. pharnaceoides in acetic acid-induced ulcerative colitis in mice and to discover the mechanism for anti-inflammatory action. Method: The ethanolic crude extract of G. pharnaceoides (Gp.Cr) was prepared and evaluated for phytochemical substances by preliminary screening and HPLC analysis. Anti-inflammatory activity of Gp.Cr (300 and 500 mg/kg) was examined by administration of 200 µl of 7.5% acetic acid intra-rectally to induce ulcerative colitis and colonic mucosal injury, while mucosal homeostasis was evaluated by disease activity index, colonic ulcer score and hematological parameters. Anti-inflammatory potential was quantified by assessing antioxidant enzymes (SOD, CAT, GPX-1), lipid peroxides, nitric oxide and cytokines (IL-1β, IL-6, TNF-α) immunoassays and further analyzed by histological analysis of colon tissues. Results: Phytochemical screening of Gp.Cr revealed the presence of alkaloids, phenols, flavonoids, steroids, tannins and saponins, while HPLC analysis confirmed the presence of quercetin, gallic acid, coumaric and sinapic acid. In acetic acid-induced ulcerative colitis model, Gp.Cr (300 and 500 mg/kg) along with sulphasalazine (500 mg/kg) decreased disease activity index, ulcer scores and hematological parameters. Gp.Cr showed a significant anti-inflammatory potential by increasing antioxidant enzymes and decreasing lipid peroxides, nitric oxide and cytokines levels. Histopathological examination showed significant decline in ulceration and tissue disruption. Conclusion: Hence, the findings confirmed the effectiveness of G. pharnaceoides crude extract in the treatment of ulcerative colitis and might be a promising remedy to manage inflammatory disorders.


Author(s):  
Abeer F. Mostafa ◽  
Mahmoud M. Elalfy ◽  
Ahmed Shata ◽  
Mona G. Elhadidy

AbstractObjectivesUlcerative colitis (UC) is a non-specific intestinal inflammatory disease. Several studies demonstrated that inflammation and oxidative stress play significant role in the pathogenesis of this disease. This study aimed to determine the protective effect and possible mechanism by which stevia affects the course of experimentally induced colitis.MethodsMale rats were received stevia 20, 40, 80 mg/kg/day before induction of colitis by intra-rectal administration of 2 mL of 4% acetic acid, AA. Macroscopic and histopathological examination of the colon were done. Colonic content of catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), myeloperoxidase (MPO) and thiobarbituric acid reactive substances (TBARS) activities and serum levels of interleukin (IL)1- β and tumor necrosis factor (TNF)-α were assessed. Real time-PCR (RT-PCR) was done to determine the expression of NF-κB, Nrf2 and PPARγ genes. Spontaneous contraction and effects of increasing concentrations of acetylcholine and stevia have been studied on the isolated colonic segments.ResultsStevia ameliorated colitis not only histopathologically but also it decreased the level of TNF-α, IL-1β, TBARS, MPO and the expression of NF-κB which were significantly increased in the AA group. The concentration of GSH, SOD, CAT and expression of Nrf2 and PPARγ were significantly increased with stevia. Moreover, stevia showed a relaxant effect on the colonic contractility which was increased in AA group. These all effects of stevia were more prominent with its highest dose.ConclusionOur results explored that, stevia acts protectively against UC by its anti-inflammatory and antioxidant properties which mediated by up-regulation of Nrf2 and PPARγ with downregulation of NF-κB. We suggest that stevia has the potential for treatment of chronic inflammatory diseases, such as UC.


2021 ◽  
Vol 20 (10) ◽  
pp. 2213-2218
Author(s):  
Lina Wei ◽  
Hua Xu

Purpose: To determine the curative impact of mesalazine (MSZ)-BTVCs combination on ulcerative colitis (UC), and its influence on inflammation and oxidative stress in the patients.Methods: 100 UC patients were randomely assigned to a control group given MSZ capsule treatment only, and a combination group treated with BTVCs and MSZ. Treatment effectiveness, inflammatory response, and oxidative stress in the two groups before and after treatment were compared.Results: The combination group had higher total effectiveness than the control group. The serum levels of MDA, high-sensitivity C-reactive protein (hs-CRP), TNF-α and interleukin-6 (IL-6) were lower, while serum levels of superoxide dismutase (SOD) and interleukin-10 (IL-10) were markedly increased in patients given combination treatment, when compared with controls. Pre-drug exposure UC disease activity index (UC-DAI) and clinical symptom scores were similar in both cohorts of patients, but the post-treatment scores were statistically decreased, especially in the combination group.Conclusion: The combined use of MSZ and BTVCs was more effective against UC than monotherapy, as it effectively relieved inflammation and oxidative stress in patients, resulting in better clinical efficacy.


2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
George Owusu ◽  
David D. Obiri ◽  
George K. Ainooson ◽  
Newman Osafo ◽  
Aaron O. Antwi ◽  
...  

Background. Ulcerative colitis (UC) is a recurrent inflammatory bowel disease (IBD) that causes long-lasting inflammation on the innermost lining of the colon and rectum. Leaf decoctions of Cordia vignei have been used in traditional medicine either alone or in combination with other plant preparations to treat the disease. Aim. In this study, we investigated the effect of hydroethanolic extract of Cordia vignei leaves (CVE) on acetic acid-induced UC in rats. Method. Male Sprague Dawley rats received oral treatment of either saline (10 ml/kg), sulfasalazine (500 mg/kg), or CVE (30-300 mg/kg) daily for 7 days. On day 4, colitis was induced by a single intrarectal administration of 500 μl of acetic acid (4% v/v). Rats were sacrificed on day 8 and colons were collected for histopathological examination. Blood was also collected for haematological assessment. Results. CVE significantly (P < 0.05) prevented colonic ulceration and reduced the inflammatory score. Serum levels of TNF-α and IL-6 were significantly reduced. Depletion of superoxide dismutase (SOD) and catalase (CAT) activities by acetic acid was significantly inhibited while lipid peroxidation indexed as malondialdehyde (MDA) level in the colon was reduced. However, loss of body weight was not significantly affected by treatment with CVE. Conclusion. This data suggest that CVE has a potential antiulcerative effect.


Author(s):  
Nurettin TUNC ◽  
abdurahman SAHİN ◽  
Ulvi DEMİREL ◽  
Gokhan ARTAS ◽  
Kazım SAHİN ◽  
...  

IntroductionIn the context of the present study, we have aimed to examine the effects of the administration of whey protein through rectal enema to a acetic acid-induced ulcerative colitis in rats on the pathways of nuclear-related factor-2 (Nrf-2), heme oxygenase-1 (HO-1), nuclear factor kappa B (NF-κB), active protein kinase-1 (AP-1), tumour necrotising factor-alpha (TNF-α), and cyclooxygenase-2 (COX-2), IL-6, IL-10.Material and methods28 rats were employed for the trial. Ulcerative colitis was induced through the use of acetic acid. The therapeutic doses of whey protein were administered rectally. Ulcerative colitis was made subject to histopathological examination and protein levels in colon tissue measured with the Western Blot Method.ResultsThe significant increases observed in the levels of AP-1, COX-2, IL-6, IL-10, NF-κβ, and TNF-α as markers of inflammation following the development of ulcerative colitis enjoyed remarkable decreases along with the administration of whey protein (p<0.05). On the other hand, we identified a decrease in the Nrf2-ARE signal pathway and HO-1 protein assuming protective roles on the colon inflammatory response along with the development of ulcerative colitis and an activation of the Nrf2-HO-1 pathway by the whey protein.ConclusionsWhey protein modulates Nrf2/HO-1 and NF-kB pathways, thereby creating a therapeutic effect against colonic inflammation induced by acetic acid (AA) by reason of its anti-inflammatory implications.


2018 ◽  
Vol 132 (9) ◽  
pp. 985-1001 ◽  
Author(s):  
Vanessa Prieto-Vicente ◽  
Ana I. Sánchez-Garrido ◽  
Víctor Blanco-Gozalo ◽  
Miguel Arévalo ◽  
Enrique García-Sánchez ◽  
...  

Cardiotrophin-1 (CT-1) holds potent anti-inflammatory, cytoprotective, and anti-apoptotic effects in the liver, kidneys, and heart. In the present study, the role of endogenous CT-1 and the effect of exogenous CT-1 were evaluated in experimental ulcerative colitis. Colitis was induced in CT-1 knockout and wild-type (WT) mice by administration of dextran sulphate sodium (DSS) in the drinking water during 7 days. CT-1 knockout mice showed higher colon damage and disease severity than WT mice. In addition, CT-1 (200 µg/kg/day, iv) or vehicle (as control) was administered during 3 days to WT, colitic mice, starting on day 4 after initiation of DSS. Disease activity index (DAI), inflammatory markers (tumor necrosis factor α (TNF-α), INFγ, IL-17, IL-10, inducible nitric oxide synthase (iNOS)), colon damage, apoptosis (cleaved caspase 3), nuclear factor κB (NFκB) and STAT-3 activation, and bacterial translocation were measured. Compared with mice treated with DSS, mice also treated with exogenous CT-1 showed lower colon damage, DAI, plasma levels of TNFα, colon expression of TNF-α, INFγ, IL-17, iNOS and cleaved caspase 3, higher NFκB and signal transducer and activator of transcription 3 (STAT3) pathways activation, and absence of bacterial translocation. We conclude that endogenous CT-1 plays a role in the defense and repair response of the colon against ulcerative lesions through an anti-inflammatory and anti-apoptotic effect. Supplementation with exogenous CT-1 ameliorates disease symptoms, which opens a potentially new therapeutic strategy for ulcerative colitis.


Marine Drugs ◽  
2018 ◽  
Vol 16 (9) ◽  
pp. 318 ◽  
Author(s):  
Alessandra Lucena ◽  
Cássio Souza ◽  
Jéssica Jales ◽  
Paulo Guedes ◽  
George de Miranda ◽  
...  

Caulerpin (CLP), an alkaloid from algae of the genus Caulerpa, has shown anti-inflammatory activity. Therefore, this study aimed to analyze the effect of CLP in the murine model of peritonitis and ulcerative colitis. Firstly, the mice were submitted to peritonitis to evaluate which dose of CLP (40, 4, or 0.4 mg/kg) could decrease the inflammatory infiltration in the peritoneum. The most effective doses were 40 and 4 mg/kg. Then, C57BL/6 mice were submitted to colitis development with 3% dextran sulfate sodium (DSS) and treated with CLP at doses of 40 and 4 mg/kg. The disease development was analyzed through the disease activity index (DAI); furthermore, colonic tissue samples were submitted to histological analysis, NFκB determination, and in vitro culture for cytokines assay. Therefore, CLP at 4 mg/kg presented the best results, triggering improvement of DAI and attenuating the colon shortening and damage. This dose was able to reduce the TNF-α, IFN-γ, IL-6, IL-17, and NFκB p65 levels, and increased the levels of IL-10 in the colon tissue. Thus, CLP mice treatment at a dose of 4 mg/kg showed promising results in ameliorating the damage observed in the ulcerative colitis.


2021 ◽  
Vol 210 (4) ◽  
pp. 275-292
Author(s):  
Hasnaa Ali Ebrahim ◽  
Dalia Mahmoud Abdelmonem Elsherbini

Ulcerative colitis (UC) is a chronic inflammatory bowel disease associated with intestinal epithelial barrier impairment. Polydatin (PD), a natural product isolated from <i>Polygonum cuspidatum</i>, is known to have an anti-inflammatory, antioxidant, and antiapoptotic effect. We attempted to compare the protective impact of PD pretreatment on alterations to the intestinal epithelial barrier and the colonic wall’s ultrastructure accompanying ulcerative colitis to other conventional drugs in practice, primarily L-carnosine, which has not been addressed before. The rats were divided into 5 groups; 3 of them were treated with sulphasalazine (500 mg/kg), L-carnosine (30 mg/kg), and PD (45 mg/kg). All groups were administered their respective drugs 3 days before the UC was induced by acetic acid intra-rectally, and the treatment was continued until the 11th day. The disease activity index (DAI) was estimated, and a macroscopic scoring was established for the harvested colonic tissue. The tissues were extracted and processed for hematoxylin and eosin staining, caspase-3 immunohistochemical staining, electron microscopy, and biochemical analysis evaluating proinflammatory markers (IL-1β, TNF-α, and IL-6), myeloperoxidase (MPO), oxidative stress, and lipid peroxidation. Histopathological examination of colonic tissue showed that PD pretreatment effectively restored mucosal epithelial cells, intercellular tight junctions, goblet cells, and maintained the intestinal epithelial and endothelial barriers. PD suppressed MPO, proinflammatory markers, and malondialdehyde but enhanced superoxide dismutase and glutathione levels. It also hampered apoptosis, as evidenced by a reduction in caspase-3 expression. PD showed a significantly better response in preserving the intestinal epithelial barrier against acetic acid-induced colitis as compared to sulphasalazine and L-carnosine. These findings demonstrate the therapeutic role of PD for patients with UC.


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